10-48453622-A-G

Position:

• chr10-48453622-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021226.4(ARHGAP22):​c.867-197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,214 control chromosomes in the GnomAD database, including 56,526 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (56526 hom., cov: 34)
• Consequence: ARHGAP22 NM_021226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

Genes affected

ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ARHGAP22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.867-197T>C		intron_variant		ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.867-197T>C		intron_variant		1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128983 AN: 152098 Hom.: 56510 Cov.: 34

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.848 AC: 129038 AN: 152214 Hom.: 56526 Cov.: 34 AF XY: 0.853 AC XY: 63468 AN XY: 74432

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.864

Alfa AF: 0.927 Hom.: 59762

Bravo AF: 0.836

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.4
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4838592; hg19: chr10-49661665;